Diisopropylethylamine → [2-[8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1 (7)-en-2-yl]ethyl]-phosphonic acid bis[1-(benzoyloxy)ethyl]ester

HRID 852472Notes

Reaction equation

HRID 852472 reaction equation
[O:1]=[C:2]1[C:10](=[O:11])[C:9]2[N:8]([CH2:12][CH2:13][P:14](=[O:17])([OH:16])[OH:15])[CH2:7][CH2:6][CH2:5][NH:4][C:3]1=2.C(N(CC)[CH:22]([CH3:24])[CH3:23])(C)C.Cl[CH:28]([O:30][C:31](=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH3:29]>CN(C=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[C:31]([O:30][CH:28]([O:17][P:14]([CH2:13][CH2:12][N:8]1[CH2:7][CH2:6][CH2:5][NH:4][C:3]2[C:2](=[O:1])[C:10](=[O:11])[C:9]1=2)(=[O:15])[O:16][CH:28]([O:30][C:31](=[O:38])[C:23]1[CH:22]=[CH:24][CH:37]=[CH:32][CH:33]=1)[CH3:29])[CH3:29])(=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 6918236PerzinfotelHCID 148941771-Chloroethyl benzoate

Product 1

HCID 11432900[2-[8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1 (7)-en-2-yl]ethyl]-phosphonic acid bis[1-(benzoyloxy)ethyl]ester

Reagents, catalysts & solvents 2

HCID 311Citric AcidSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of the starting [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]phosphonic acid (19.22 mmol, 5 g) in dry DMF (100 mL) was treated with N,N-diisopropylethylamine (76.88 mmol, 13.39 mL). The reaction mixture was stirred for 30 minutes at ambient temperature after which benzoic acid-1-chloroethyl ester (57.66 mmole, 10.65 g, synthesis described below) was added. The mixture was then stirred at 70° C. for 36 hours, cooled to ambient temperature and diluted with citric acid (2% aqueous solution, 70 mL). The product was extracted with ethyl acetate (3×50 mL), washed with sodium bicarbonate (3%) and brine. The organic layer was dried over magnesium sulfate, filtered, and evaporated to dryness. The residue was flash chromatographed on silica gel. Elution with a gradient of 2 to 8% methanol in chloroform afforded 1.66 g (15.5%) of a stereoisomer of [2-[8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethyl]-phosphonic acid bis[1-(benzoyloxy)ethyl]ester (example 8) [MS (ES+): m/e 557 (M+H)] and 0.73 g (6.8%) of a less polar diastereoisomer of [2-[8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethyl]-phosphonic acid bis[1-(benzoyloxy)ethyl]ester (example 9) [MS (ES+): m/e 557 (M+H)].

Workup

  1. additionwas added
  2. temperaturecooled to ambient temperature
  3. extractionThe product was extracted with ethyl acetate (3×50 mL)
  4. washwashed with sodium bicarbonate (3%) and brine
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customchromatographed on silica gel
  9. washElution with a gradient of 2 to 8% methanol in chloroform

Sources & evidence

ORD record
ord-a4ef9d08751b42d7bf4595bf86218633
Source dataset
uspto-grants-2007_08
Patent number
US07253153B2

Reaction notes

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